Since its first publication in 1977, the World Health Organization’s (WHO) Model List of Essential Medicines (EML) has guided the national procurement of medicines deemed essential to inform public health policy worldwide. Aiming to include the most effective, safe, and cost-effective medicines for priority conditions, WHO updates the EML every two years. However, over the past 45 years, updates to the mental health section of the EML have been infrequent, mostly involving the addition of individual medicines. A comprehensive revision of the entire section was never attempted.

The aim of this project was to update the mental health section of the EML to identify the most effective and safest medicines for mental disorders in the light of the most up-to-date evidence base.

A series of nine evidence-based applications were submitted to the WHO Expert Committee on the Selection and Use of Essential Medicines in December 2022, recommending a substantial revision of the entire mental health section.

All of our applications were accepted by the WHO Expert Committee. For psychotic disorders, aripiprazole, olanzapine, paliperidone, and quetiapine were added as therapeutic alternatives to risperidone; short-acting intramuscular chlorpromazine was replaced by short-acting intramuscular olanzapine; first-generation antipsychotics were limited to oral haloperidol and chlorpromazine. For bipolar disorder, the list now includes second-generation antipsychotics such as quetiapine, aripiprazole, olanzapine, and paliperidone. Tricyclic antidepressants for depressive disorders were limited to amitriptyline alone. Treatment options for anxiety and obsessive-compulsive disorder are now expanded to include SSRIs. For anxiety disorders, diazepam and lorazepam became the only benzodiazepines recommended, with the specific caveat that they should only be used for short-term emergency treatment of acute and severe anxiety symptoms. Finally, chlorpromazine and haloperidol are no longer considered essential medications for psychotic disorders in children under 13 years of age.

The WHO released the 23rd EML in July 2023. After decades of minimal and inconsistent updates, groundbreaking changes have been made to its mental health section. The updated mental health section provides a compelling opportunity to improve the quality of medicine selection at the country level, with the goal of increasing the availability of the safest and most effective psychotropic medicines worldwide.

None Declared

Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatment choices for GAD, but which should be considered as first-line treatment still needs to be clarified.

To examine the most effective and accepted psychotherapy for GAD both in the short and long-term, via a network meta-analysis.

We searched MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials – CENTRAL, from database inception to January 1st, 2023, to find randomized controlled trials (RCTs) of psychotherapies for GAD. Eight psychotherapies (behaviour therapy, cognitive-behaviour therapy, cognitive restructuring, psychoeducation, psychodynamic therapy, relaxation therapy, supportive psychotherapy, and third-wave CBTs) were compared with each other and two control conditions (treatment as usual, waiting list). We followed Cochrane standards when extracting data and assessing data quality and used PRISMA guidelines for the reporting. We conducted random-effects model pairwise and network meta-analyses. We assessed risk of bias of individual studies through the second version of the Cochrane’s Risk of Bias tool and used the Confidence in Network Meta-Analysis (CINeMA) to rate certainty of evidence for meta-analytical results. Severity of GAD symptoms and acceptability of the psychotherapies were our outcomes of interest.

We analysed data from 66 RCTs. Effect size estimates on data from 5,597 participants suggest third wave cognitive-behavioural therapies (standardized mean differences [SMDs] =-0.78; 95%CI=-1.19 to -0.37; certainty=moderate), cognitive-behavioural therapy (CBT) (SMD=-0.68; 95%CI=-1.05 to -0.32 certainty=moderate), and relaxation therapy (SMD=-0.54; 95%CI=-1.04 to -0.05; certainty=low) reduced generalized anxiety symptoms more than treatment as usual (TAU). Relative risks for all-cause discontinuation signalled no differences compared with TAU for all psychotherapies. When excluding studies at high risk of bias, relaxation therapy lost its superiority over TAU. When considering anxiety severity at three to twelve months after completion of the intervention only CBT remained significantly more efficacious than TAU (SMD=-0.58; 95%CI=-0.93 to -0.23).

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Given the evidence for both acute and long-term efficacy, CBT may represent the reasonable first-line psychological treatment for GAD. Third-wave CBT and relaxation therapy have short-term efficacy and may also be offered. Results from this investigation should inform patients, clinicians, and guidelines. This project is funded by the European Union’s HORIZON EUROPE research programme under grant agreement No 101061648.

None Declared

Antidepressant discontinuation may cause withdrawal syndrome in some cases. However, evidence on this syndrome related to individual antidepressants is limited, as well as about individual risk factors for severe reactions.

To ascertain whether each individual antidepressant is associated with an increased reporting of withdrawal syndrome as compared with other medications, and to examine clinical risk factors for severe reactions.

We conducted a pharmacovigilance study, with a case/non-case design. We included reports of antidepressant-related withdrawal syndrome from the VigiBase, the WHO global database of individual case safety reports of suspected adverse drug reactions. We performed a disproportionality analysis (calculating reporting odds ratio (ROR) and the Bayesian information component (IC)) of reports of antidepressant-related withdrawal syndrome, comparing antidepressants to all other drugs and to buprenorphine (as a positive control). Antidepressants with significant disproportionate reporting were ranked in terms of clinical priority. We compared serious versus non-serious reactions to determine clinical risk factors for severe reactions.

Based on 31,688 reports of antidepressant-related withdrawal syndrome, we detected a disproportionate reporting for 23 antidepressants. The ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95%CI:14.08-14.45), 17.01 for other antidepressants (95%CI:16.73-17.29), 13.65 for SSRIs (95%CI:13.41-13.90) and 2.8 for tricyclics (95%CI:2.59-3.02). Based on clinical priority ranking, the strongest signals were found for paroxetine, duloxetine, venlafaxine and desvenlafaxine (figure 1), being comparable to buprenorphine. Severe reactions were more frequently reported in males, adolescents, persons with multiple medications, and with longer treatment duration.

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Antidepressants are associated with increased reporting of withdrawal syndrome compared with other medications, with differences between individual antidepressants. Clinicians should be aware of such differences, when prescribing and discontinuing these drugs, as well as of the risk to experience more severe withdrawal symptoms in specific cases.

C. Gastaldon: None Declared, G. Schoretsanitis Consultant of: Dr. Schoretsanitis has served as a consultant for HLS Therapeutics, E. Arzenton : None Declared, E. Raschi : None Declared, D. Papola: None Declared, G. Ostuzzi: None Declared, U. Moretti: None Declared, E. Seifritz Grant / Research support from: Dr. Seifritz has received educational grants, consulting fees and lecture honoraria from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Ricordati, Vifor, Sunovion, Schwabe and Mepha, Consultant of: Dr. Seifritz has received educational grants, consulting fees and lecture honoraria from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Ricordati, Vifor, Sunovion, Schwabe and Mepha, J. Kane Shareolder of: LB Pharmaceuticals and Vanguard Research Group, Consultant of: Dr. Kane has been a consultant and/or advisor for or has received honoraria from Alkermes, Allergan, LB Pharmaceuticals, H. Lundbeck, Intracellular Therapies, Janssen Pharmaceuticals, Johnson and Johnson, Merck, Minerva, Neurocrine, Newron, Otsuka, Pierre Fabre, Reviva, Roche, Sumitomo Dainippon, Sunovion, Takeda, Teva and UpToDate, G. Trifirò Grant / Research support from: he was the scientific director of a Master program on pharmacovigilance, pharmacoepidemiology and real-world evidence which has received non-conditional grant from various pharmaceutical companies; he coordinated a pharmacoepidemiology team at the University of Messina until Oct 2020, which has received funding for conducting observational studies from various pharmaceutical companies (Boehringer Ingelheim, Daichii Sankyo, PTC Pharmaceuticals). He is also scientific coordinator of the academic spin-off “INSPIRE srl” which has received funding for conducting observational studies from contract research organizations (RTI Health Solutions, Pharmo Institute N.V.)., Consultant of: Dr. Trifirò has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen;, Speakers bureau of: Dr. Trifirò has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen;, C. Barbui: None Declared

Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitors (SSRIs).

To ascertain whether maternal antidepressant treatment may be associated with withdrawal syndrome in neonates, investigating the comparative reporting between individual antidepressants and classes.

We performed a case/non-case pharmacovigilance study, searching reports of withdrawal syndrome in newborns in the VigiBase, the WHO database of suspected adverse drug reactions. Disproportionality analysis was performed, estimating reporting odds ratio (ROR) and the Bayesian information component (IC). Antidepressants were compared to all other medications, to methadone, and within each class of antidepressants (SSRIs, tricyclics (TCA) and other antidepressants). Antidepressants were ranked in terms of clinical priority, based on a semiquantitative score.

We retrieved 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants. Compared to all other drugs, disproportionate reporting was detected for antidepressants altogether (ROR: 6.18, 95%CI:5.45-7.01), for TCAs (10.55, 95%CI:8.02-13.88), other antidepressants (ROR: 5.90, 95%CI:4.74-7.36) and SSRIs (ROR: 4.68, 95%CI:4.04-5.42). All antidepressants showed a significant disproportionality, apart from bupropion (figure 1). We did not find any disproportionate reporting for any antidepressant compared to methadone. The clinical priority ranking showed moderate clinical priority for all antidepressants, with the exception four, that had a weak one (figure 1). Most frequently reported symptoms were respiratory symptoms (n=106), irritability/agitation (n=75), tremor (n=52) and feeding problems (n=40).

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Exposure to antidepressants in utero is associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome for most antidepressants. Clinicians should pay extra attention to neonates with antidepressant-treated mothers.

C. Gastaldon: None Declared, E. Arzenton : None Declared, E. Raschi: None Declared, O. Spigset: None Declared, D. Papola: None Declared, G. Ostuzzi: None Declared, U. Moretti: None Declared, G. Trifirò Grant / Research support from: he was the scientific director of a Master program on pharmacovigilance, pharmacoepidemiology and real-world evidence which has received non-conditional grant from various pharmaceutical companies; he coordinated a pharmacoepidemiology team at the University of Messina until Oct 2020, which has received funding for conducting observational studies from various pharmaceutical companies (Boehringer Ingelheim, Daichii Sankyo, PTC Pharmaceuticals). He is also scientific coordinator of the academic spin-off “INSPIRE srl” which has received funding for conducting observational studies from contract research organizations (RTI Health Solutions, Pharmo Institute N.V.)., Consultant of: has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen, Speakers bureau of: has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen, C. Barbui: None Declared, G. Schoretsanitis Consultant of: Dr. Schoretsanitis has served as a consultant for HLS Therapeutics and Thermo Fisher Scientific.

Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs).

In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared.

A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45–7.01, IC: 2.07, 95% CI 1.92–2.21). Signals were found for TCAs (10.55, 95% CI 8.02–13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74–7.36) and SSRIs (ROR: 4.68, 95% CI 4.04–5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40).

Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.

As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe.

Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ⩾ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes.

Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389–1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180–1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001).

The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.

To provide a cross-country analysis of selection, availability, prices and affordability of essential medicines for mental health conditions, aiming to identify areas for improvement.

We used the World Health Organization (WHO) online repository of national essential medicines lists (EMLs) to extract information on the inclusion of essential psychotropic medicines within each country's EML. Data on psychotropic medicine availability, price and affordability were obtained from the Health Action International global database. Additional information on country availability, prices and affordability of essential medicines for mental disorders was identified by searching, up to January 2021, PubMed/Medline, CINAHIL, Scopus and the WHO Regional Databases. We summarised and compared the indicators across lowest-price generic and originator brand medicines in the public and private sectors, and by country income groups.

A total of 112 national EMLs were analysed, and data on psychotropic medicine availability, price and affordability were obtained from 87 surveys. While some WHO essential psychotropic medicines, such as chlorpromazine, haloperidol, amitriptyline, carbamazepine and diazepam, were selected by most national lists, irrespective of the country income level, other essential medicines, such as risperidone or clozapine, were included by most national lists in high-income countries, but only by a minority of lists in low-income countries. Up to 40% of low-income countries did not include medicines that have been in the WHO list for decades, such as long-acting fluphenazine, lithium carbonate and clomipramine. The availability of generic and originator psychotropic medicines in the public sector was below 50% for all medicines, with low-income countries showing rates lower than the overall average. Analysis of price data revealed that procurement prices were lower than patient prices in the public sector, and medicines in the private sector were associated with the highest prices. In low-income countries, the average patient price for amitriptyline and fluoxetine was three times the international unit reference price, while the average patient price for diazepam was ten times the international unit reference price. Affordability was higher in the public than the private sector, and in high-income than low-income countries.

Access to medicines for mental health conditions is an ongoing challenge for health systems worldwide, and no countries can claim to be fully aligned with the general principle of providing full access to essential psychotropic medicines. Low availability and high costs are major barriers to the use of and adherence to essential psychotropic medicines, particularly in low-and middle-income countries.

People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but the underlying medical condition and possible interaction with medical treatments might pose serious safety issues.

To review the direct and indirect evidence on the safety of psychotropic drugs in people with COVID-19 and provide practical recommendations for frontline clinicians.

An international, multi-disciplinary working group was established with the aim of producing evidence-based recommendations on the management of psychotropic medications in people with COVID-19, following the WHO Rapid Advice Guidelines methodology in the context of a public health emergency. Evidence retrieved was focused on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications. Furthermore, drug-drug interactions between psychotropic and medical treatments used in people with COVID-19 was reviewed and critically discussed by the working group.

The analysis of available evidence, although indirect, showed that all classes of psychotropic medications might carry relevant safety risks for people with COVID-19. The working group produced a set of 12 recommendations to support clinicians in the assessment of the anticipated risk of psychotropic-related unfavourable events, and how to practically manage this risk, including when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication.

The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.

No significant relationships.

Panic disorder is among the most prevalent anxiety diseases. Although psychotherapy is recommended as first-line treatment for panic disorder, little is known about the relative efficacy of different types of psychotherapies.

To evaluate the effectiveness and acceptability of different types of psychotherapies for adults suffering from panic disorder, with or without agoraphobia.

We are conducting a systematic network meta-analysis of randomized controlled trials examining panic disorder. A comprehensive search was performed to identify relevant studies. The primary efficacy outcome is anxiety symptoms at study endpoint. The primary acceptability outcome is all-cause trial discontinuation at endpoint. Pairwise and network meta-analysis will be conducted. We are considering any kind of psychotherapy delivered by any therapist, as long as they were trained to deliver the therapy, or as self-help.

To date we have identified 126 panic disorder and agoraphobia trials. The publication time span ranges from 1968 to 2020. We are now extracting data to provide an overview of the included study characteristics. The statistical analysis will be conducted between December 2020 and January 2021, and its results presented for the first time at the forthcoming 2021 EPA congress.

126 trials on psychotherapy for panic disorders in adults are available. Because of this huge body of knowledge, it is important that the results of these studies are summarized using network meta-analytic techniques. The findings of this study will guide future research as knowledge gaps will be easily identified. Moreover, policymakers will have the opportunity to use this summarized knowledge to inform evidence-based decision making.

No significant relationships.

QTc interval prolongation is considered a risk factor for fatal polymorphic ventricular tachycardia, which can result in sudden cardiac death. Most psychotropic drugs have a dose-dependent potential to prolong the QTc interval. However, other factors require appropriate consideration, including: age; gender; other medications; electrolyte abnormalities; severe comorbid conditions, such as co-occurring alcohol or substances abuse/dependence.

The objective was to study the potential mediating roles of alcohol/substances abuse on QTc prolongation.

The Italian research group STAR Network, in collaboration with the Young Italian Psychiatrists Association, aimed to evaluate the frequency of QTc interval prolongation in a sample of patients under treatment with psychotropic drugs through a cross-sectional national survey.

A sample of 2411 unselected patients were enrolled after performing an ECG during the recruitment period. Sociodemographic and clinical characteristics were collected from medical records. Collected data underwent statistical analysis.

A total of 11.2% of patients reported alcohol abuse, and only 8.9% psychotropic substances. According to the threshold, less than 20% of patients had a borderline value of QTc, and 1% a pathological value. Patients with co-occurring alcohol misuse and drug abuse were more likely to have longer QTc interval.

The present study describes the frequency of QTc prolongation in real-world clinical practice. Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The potential role of alcohol and substances on QTc length could be particularly useful in emergency settings.

The authors have not supplied their declaration of competing interest.

In the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers.

We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason.

We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = −0.71; 95% confidence interval [CI] −1.01 to −0.41; I2 = 83%; 95% CI 78–88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = −1.02; 95% CI −1.52 to −0.51; I2 = 89%; 95% CI 82–93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = −1.05; 95% CI −1.55 to −0.56; I2 = 87%; 95% CI 79–92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life.

Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.